Three new 18,19-seco-ursane glycosides from Elsholtzia bodinieri

Chromatographic separation of an extract of the aerial part of Elsholtzia bodinieri resulted in the isolation of three new 18,19-seco-ursane glycosides, bodiniosides E-G (1–3). Their structures were elucidated as 2α,12β,23-trihydroxy-3-(β-d-glucopyranosyl)-19-oxo-18,19-seco-urs-13(18)-en-28-O-β-d-glucopyranosyl ester (1), 3-β-d-glucopyranosyl-19-β-d-glucopyranosyl-12β,21-dihydroxy-18,19-seco-urs-13(18)-en-28-oic acid (2), and 2α,12β,21-trihydroxy-3-β-d-glucopyranosyl-19-β-d-glucopyranosyl-18,19-seco-urs-13(18)-en-28-oic acid (3), respectively, by extensive NMR techniques, including 1D- and 2D-NMR experiments, as well as comparing with spectral data with those of the known analogues.     

Triterpenoid profile and bioactivity study of Oenothera maritima

Four new triterpenoids, 2α,3α,20β,23-tetrahydroxy-ursa-12,19(29)-dien-28-oic acid (1), 2α,3α,20β,23-tetrahydroxy-ursa-12,19(29)-dien-28,20β-lactone (2), 2α,3α-dihydroxy-ursa-12,19-dien-28-oic acid 28-O-β-d-glucopyranoside (3) and 2α,3α,23-trihydroxy-ursa-12,19(29)-dien-28-oic acid (4) together with six known compounds (5–10), were isolated from the aerial parts of Oenothera maritima Nutt. Their structures were elucidated on the basis of spectroscopic data and chemical methods. Compounds 1, 3–10 were evaluated for their in vitro thrombin inhibitory activity and their selectivity against factor Xa and trypsin.     

Seven new triterpenoids from the aerial parts of Ilex cornuta and protective effects against H2O2-induced myocardial cell injury

Seven new triterpenoids (1–7), together with two known ones (8–9), were isolated from the aerial parts ofIlex cornuta. The leaves of I. cornuta are the major source of “Kudingcha”, a popular herbal tea consumed in China and other countries. The structures of compounds 1–7 were determined as 20-epi-urs-12,18-dien-28-oic acid 3β-O-α-l-arabinopyranoside (1), 20-epi-urs-12,18-dien-28-oic acid 2′-O-acetyl-3β-O-α-l-arabinopyranoside (2), 20-epi-urs-12,18-dien-28-oic acid 3β-O-β-d-glucuronopyranoside-6-O-methyl ester (3), 3β,23-dihydroxy-20-epi-urs-12,18-dien-28-oic acid (4), 23-hydroxy-20-epi-urs-12,18-dien-28-oic acid 3β-O-α-l-arabinopyranoside (5), 23-hydroxy-20-epi-urs-12,18-dien-28-oic acid 3β-O-β-d-glucuronic acid (6), 23-hydroxy-20-epi-urs-12,18-dien-28-oic acid 3β-O-β-d-glucuronopyranoside-6-O-methyl ester (7), on the basis of spectroscopic analyses (IR, ESI–MS, HR-ESI–MS, 1D and 2D NMR) and chemical reactions. Protective effects against H₂O₂-induced H9c2 cardiomyocyte injury were tested in vitro for compounds 1–9, and the data showed that compound 4 had significant cell-protective effect. Compounds 1-9 did not show significant DPPH radical scavenging activity.     

Novel biotransformation processes of dihydroartemisinic acid and artemisinic acid to their hydroxylated derivatives by two plant cell culture systems

Novel biotransformation processes of dihydroartemisinic acid (1) and artemisinic acid (2) to their hydroxylated derivatives were investigated using the cell suspension cultures of Catharanthus roseus and Panax quinquefolium crown galls as two biocatalyst systems. Five biotransformation products, 3-α-hydroxydihydroartemisinic acid (3), 3-β-hydroxydihydroartemisinic acid (4), 15-hydroxy-cadin-4-en-12-oic acid (5), 3-α-hydroxyartemisinic acid (6) and 3-β-hydroxyartemisinic acid (7), were isolated by chromatograph methods and identified by the analysis of ¹H NMR, ¹³C NMR, and ESI-MS spectra. Compounds 3–5 were obtained for the first time by biotransformation process. It was also the first time to transform artemisinic acid to yield epimeric 3-hydroxy artemisinic acids in plant cell culture system. The biocatalyst system of C. roseus cell cultures showed a great capacity of regio- and stereo-selective hydroxylation in allyl group of the exogenous substrates. The results also showed that the biocatalyst system of P. quinquefolium crown galls possessed the ability to hydroxylate propenyl group of exogenous substrates in a regio- and substrate-selective manner. Furthermore, the in vitro antitumor activity of the hydroxyl products was evaluated by MTT assay. The result indicated that α-hydroxyl products possessed stronger antitumor activity than β-hydroxyl products against the HepG2 and GLC-82 cell lines.     

Tricyclic diterpenes from the resin of Daemonorops draco and their activities on oxidative stress-induced mesenchymal stromal cells

A bioassay-guided chemical investigation of the resin exudates from Daemonorops draco (dragon’s blood, Palmaceae) has resulted in the isolation of two new trinorditerpenes, 7β-13-dihydroxypodocarpa-8,11,13-trien-15-oic acid (1) and 7α-13-dihydroxypodocarpa-8,11,13-trien-15-oic acid (2), along with ten previously described abietane diterpenes, 7β-15-dihydroxydehydroabietic acid (3), 7α-15-dihydroxydehydroabietic acid (4), 15-hydroxydehydroabietic acid (5), 7-oxodehydroabietic acid (6), dehydroabietic acid (7), 15-hydroxyabietic acid (8), 12α-hydroxyabietic acid (9), abietic acid (10), 7,13,15-abietatrien-18-oic acid (11), and cephasinene B (12). The structures of 1 and 2 were elucidated using spectroscopic techniques, including HR-ESIMS and 1D/2D NMR. The absolute configurations were determined by comparing the experimental electronic circular dichroism (ECD) spectra with the calculated ECD data based on time-dependent density functional theory. The bioactivity of the extracts, fractions, and isolated compounds was assessed in oxidative stress-induced mesenchymal stromal cells (MSCs). The crude extract and the hexanes, ethyl acetate, and aqueous fractions exhibited high potency against oxidative stress-induced apoptosis of MSCs. Among the isolated compounds, compounds 1 (3 μM) and 10 (100 μM) demonstrated good recovery of MSCs against oxidative stress.     

Bioactivity-guided isolation of cytotoxic triterpenoids from the trunk of Berberis koreana

A bioassay-guided fractionation and chemical investigation of the trunk of Berberis koreana resulted in the isolation and characterization of two new triterpenoids, 23-trans-p-coumaroyloxy-2α,3α-dihydroxyolean-12-en-28-oic acid (1), and 23-cis-p-coumaroyloxy-2α,3α-dihydroxyolean-12-en-28-oic acid (2), along with seven known triterpenoids (3–9). The structures of the new compounds were determined on the basis of spectroscopic analyses including 2D NMR. The cytotoxic activities of the triterpenes (1–9) were evaluated by determining their inhibitory effects on human tumor cell lines (A549, SK-OV-3, SK-MEL-2, and HCT-15) using the SRB assay. Compounds 5 and 6 showed potent cytotoxicity against A549, SK-OV-3, SK-MEL-2, and HCT-15 cell lines (IC₅₀ (5): 4.37, 7.04, 9.72, and 5.83 μM, and IC₅₀ (6): 5.57, 7.84, 13.29, and 5.61 μM, respectively).     

New alkamide and ent-kaurane diterpenoid derivatives from Senecio erechtitoides (Asteraceae)

Fractionation of a MeOH/CH₂Cl₂ (1/1) extract of the aerial parts of Senecio erechtitoides led to the isolation of six compounds including the hitherto unknown N-phenethylamide derivative named N-(p-hydroxyphenethyl)pentacosanamide (1), and a kauranoid derivative named derivative named ent-7-oxo-16α,17-dihydroxykauran-19-oic acid (2), as well as four known compounds, ent-Kaur-16-en-19-oic acid (3), ent-7β-hydroxykaur-16-en-19-oic acid (4), ent-7-oxokaur-16-en-19-oic acid (5), steppogenin 4′-O-β-d-glucoside (6). Their structures and relative configurations were elucidated on the basis of spectroscopic methods, chemical reactions, and comparison with previously known analogs. All isolates were evaluated for their antimicrobial activity and only diterpenoids were found to possess a potent inhibitor effect against the range of microorganism.     

Biotransformation of ent-pimaradienoic acid by cell cultures of Aspergillus niger

Microbial transformation stands out among the many possible semi-synthetic strategies employed to increase the variety of chemical structures that can be applied in the search for novel bioactive compounds. In this paper we obtained ent-pimaradienoic acid (1, PA, ent-pimara-8(14),15-dien-19-oic acid) derivatives by fungal biotransformation using Aspergillus niger strains. To assess the ability of such compounds to inhibit vascular smooth muscle contraction, we also investigated their spasmolytic effect, along with another five PA derivatives previously obtained in our laboratory, on aortic rings isolated from male Wistar rats. The microbial transformation experiments were conducted at 30 °C using submerged shaken liquid culture (120 rpm) for 10 days. One known compound, 7α-hydroxy ent-pimara-8(14),15-dien-19-oic acid (2), and three new derivatives, 1β-hydroxy ent-pimara-6,8(14),15-trien-19-oic acid (3), 1α,6β,14β-trihydroxy ent-pimara-7,15-dien-19-oic acid (4), and 1α,6β,7α,11α-tetrahydroxy ent-pimara-8(14),15-dien-19-oic acid (5), were isolated and identified on the basis of spectroscopic analyses and computational studies. The compounds obtained through biotransformation (2–5) did not display a significant antispasmodic activity (values ranging from 0% to 16.8% of inhibition); however the previously obtained diterpene, methyl 7α-hydroxy ent-pimara-8(14),15-dien-19-oate (8), showed to be very effective (82.5% of inhibition). In addition, our biological results highlight the importance to study the antispasmodic potential of a large number of novel diterpenes, to conduct further structure–activity relationship investigations.     

Triterpenoids from the seedpods of Holarrhena curtisii King and Gamble

Two new hydroperoxy pentacyclic triterpenoids, 3β-hydroxy-11α-hydroperoxyolean-12-en-28-oic acid (1) and 3β-hydroxy-11α-hydroperoxyursan-12-en-28-oic acid (2), together with nine known triterpenoids, squalene (3), β-amyrin acetate (4), α-amyrin acetate (5), lupeol acetate (6), lupeol (7), lanosta-7,24-dien-3β-ol (8), cycloeucalenol (9), oleanolic acid (11) and ursolic acid (12), a known phytosterol, 24-methylenepollinastanol (10), and two known flavanols, (–)-catechin (13) and (–)-gallocatechin (14), were isolated from the methanolic extract of the fresh seedpods of Holarrhena curtisii. Their structures were determined by spectroscopic analysis (one and two dimensional nuclear magnetic resonance, high resolution electrospray ionization mass spectrometry and attenuated total reflectance-Fourier transform infrared spectroscopy). All compounds (except squalene) were evaluated for their in vitro α-glucosidase inhibitory activity. Compounds 1, 2, 11 and 12, which had a pentacyclic triterpenoid acid skeleton, showed a strong in vitro α-glucosidase inhibitory activity compared to that of the standard control, acarbose.     

Isopimarane diterpene glycosides, apoptosis inducers, obtained from fruiting bodies of the ascomycete Xylaria polymorpha

The methanol extract of fruiting bodies of the ascomycete Xylaria polymorpha afforded three isopimarane diterpene glycosides, namely, 16-α-d-mannopyranosyloxyisopimar-7-en-19-oic acid (1), 15-hydroxy-16-α-d-mannopyranosyloxyisopimar-7-en-19-oic acid (2), and 16-α-d-glucopyranosyloxyisopimar-7-en-19-oic acid (3). Their structures were determined by spectroscopic methods and by single-crystal X-ray analysis. They showed cytotoxicity against human cancer cell lines and exhibited IC₅₀ values ranging from 71 to 607 μM. Further studies on the cytotoxicity of these compounds against HL60 cells demonstrated that they induced apoptosis along with typical DNA fragmentation. It was observed that 2 was less active than 1 and 3.     

Selective oxidation-reduction and esterification of asiatic acid by Pestalotiopsis microspora and anti-HCV activity

Microbial transformation of asiatic acid (AA) by an endophytic fungus, Pestalotiopsis microspora, yielded six metabolites: 2-oxo-3β,15α,23-trihydroxyurs-12-ene-28-oic acid (1); 2-oxo-3β,15α,22α,23-tetrahydroxyurs-12-ene-28-oic acid (2); 2-oxo-3β,15α,23,30-tetrahydroxyurs-12-ene-28-oic acid (3); 2α,3β,15α,23,30-pentahydroxyurs-12-ene-28-oic acid methyl ester (4); 2α,3α,15α,23-tetrahydroxyurs-12-ene-28-oic acid (5); 2α,3α,15α,23,30-pentahydroxyurs-12-ene-28-oic acid (6). The structure elucidation of these products was confirmed based on the spectroscopic data. Compounds 2–6 were new. A possible biotransformation pathway is proposed. The anti-HCV activity of compounds 1–6 was also evaluated.     

Triterpenoidal saponins of Pulsatilla koreana roots

Sixteen (1-16) triterpenoidal saponins were isolated from the roots of Pulsatilla koreana, of which four were determined as the previously unknown 23-hydroxy-3β-[(O-α-L-arabinopyranosyl)oxy]lup-20(29)-en-28-oic acid 28-O-β-D-glucopyranosyl ester (1), 23-hydroxy-3β-[(O-α-L-rhamnopyranosyl-(1 → 2)-α-L-arabinopyranosyl)oxy]lup-20(29)-en-28-oic acid 28-O-β-D-glucopyranosyl ester (2), 3β-[(O-α-L-rhamnopyranosyl-(1 → 2)-α-L-arabinopyranosyl)oxy]lup-20(29)-en-28-oic acid 28-O-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranosyl ester (3), and 3β-[(O-α-L-rhamnopyranosyl-(1 → 2)-O-[β-D-glucopyranosyl-(1 → 4)]-α-L-arabinopyranosyl)oxy]lup-20(29)-en-28-oic acid 28-O-α-L-rhamnopyranosyl-(1 → 4)-O-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranosyl ester (4), respectively, based on spectroscopic analysis. The inhibition of the lipopolysaccharide-induced nitric oxide production of sixteen isolated compounds was evaluated in RAW 264.7 cells at concentrations ranging from 1 μM to 100 μM.     

3,4-Seco-spirostane sapogenins with cytotoxic activity from Allium umbilicatum boiss

Two new sapogenins, named seco-umbilicagenins A and B (1 and 2), possessing a new chemical structure based on a 3,4-seco-spirostane skeleton, were isolated from Allium umbilicatum Boiss. The chemical structures of seco-umbilicagenins A and B were established through a combination of extensive spectroscopic analysis, mainly nuclear magnetic resonance spectroscopy and mass spectrometry, and chemical methods as (2S,25R)-2,5α,6β-trihydroxy-3,4-seco-spirosta-3,4-dioic acid (1) and (2S,25R)-2,4,5α-trihydroxy-6-oxo-3,4-seco-spirostan-3-oic acid (2). Interestingly, the isolated compounds exhibited cytotoxic activity on J-774, murine monocyte/macrophage, and WEHI-164, murine fibrosarcoma, cell lines. To the best of our knowledge this is the first time that 3,4-seco-spirostane sapogenins are isolated from natural sources, being this skeleton obtained by synthetic modification of intact sapogenins.     

New 19α-hydroxyursane-type triterpenes from the leaves of Meyna spinosa (= Vangueria spinosa), Rubiaceae

Two new 19α-hydroxyursane-type triterpenes, 2α,3α,19α,24,28-pentahydroxyurs-12-ene (1) and meyanthic acid, 3β-acetoxy-2β,19α,23-trihydroxyurs-12-en-28-oic acid (2) along with one new aliphatic ester, myricyl pentadecanoate (3) and five known compounds, 19α-hydroxyasiatic acid (4), oleanolic acid (5), myricyl alcohol (6), β-sitosterol (7) and its glycoside (8) were isolated from the methanolic leaf extract of Meyna spinosa Roxb. ex Link (= Vangueria spinosa Roxb., Rubiaceae). The structures of the new compounds were elucidated on the basis of extensive spectroscopic (including 2D NMR) analysis and comparison with literature. Except oleanolic acid, isolation of known compounds was reported for the first time from this plant.     

A new ursane-type triterpenoid glycoside from Centella asiatica leaves modulates the production of nitric oxide and secretion of TNF-α in activated RAW 264.7 cells

One new ursane-type triterpenoid glycoside, asiaticoside G (1), five triterpenoids, asiaticoside (2), asiaticoside F (3), asiatic acid (4), quadranoside IV (5), and 2α,3β,6β-trihydroxyolean-12-en-28-oic acid 28-O-[α-l-rhamnopyranosyl-(1→4)-β-d-glucopyranosyl-(1→6)-β-d-glucopyranosyl] ester (6), and four flavonoids, kaempferol (7), quercetin (8), astragalin (9), and isoquercetin (10) were isolated from the leaves of Centella asiatica. Their chemical structures were elucidated by mass, 1D- and 2D-nuclear magnetic resonance (NMR) spectroscopy. The structure of new compound 1 was determined to be 2α,3β,23,30-tetrahydroxyurs-12-en-28-oic acid 28-O-[α-l-rhamnopyranosyl-(1→4)-β-d-glucopyranosyl-(1→6)-β-d-glucopyranosyl] ester. The anti-inflammatory activities of the isolated compounds were investigated on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Asiaticoside G (1) potently inhibited the production of nitric oxide and tumor necrosis factor-α with inhibition rates of 77.3% and 69.0%, respectively, at the concentration of 100 μM.     

Cytotoxic and anti-angiogenic effects of lanostane triterpenoids from Ganoderma lucidum

Two new lanostane triterpenes, 3α,12β,15α-triacetoxy-5α-lanosta-7,9(11),24-trien-26-oic acid (1) and 5α-lanosta-8,24-diene-26,27-dihydroxy-3,7-dione (2), together with sixteen known compounds (3–18) were isolated from the fruiting bodies of the Vietnamese mushroom Ganoderma lucidum. Their chemical structures were determined by extensive spectroscopic (IR, HR-EI-MS, 1D and 2D NMR) analyses. Potential cytotoxic activities of these compounds were evaluated against human non-small cell lung adenocarcinoma (A549), breast adenocarcinoma (MCF-7), and prostatic small cell carcinoma (PC-3). Among the compounds, 3α,12β,15α-triacetoxy-5α-lanosta-7,9(11),24-trien-26-oic acid (1) showed significant cytotoxic activity against PC-3 cells with an IC₅₀ of 11.5 μM. In studies of anti-angiogenesis activity, ganoderic acid F (17) was found to have the most potent inhibitory effect on the formation of capillary-like structures of human umbilical vein endothelial cells.     

Chemotaxonomic implications of the absence of sesquiterpene lactones in Grazielia multifida (DC.) R.M.King & H.Rob. (Asteraceae)

The phytochemical investigation of Grazielia multifida aerial parts yielded eight compounds, including four ent-kaurenic acid diterpenes derivatives, 15-tiglinoyloxy-ent-kaur-16-en-19-oic acid (1), 15-hydroxy-ent-kaur-16-en-19-oic acid (2), 17-hydroxy-ent-kaur-15-en-19-oic acid (3) and 15-isovaleroyloxy-ent-kaur-16-en-19-oic acid (4), one amino acid, tryptophan (5), and three flavonoids, eupafolin (6), guaijaverin (7) and quercitrin (8). The structures of the isolated compounds were established based on analysis of their spectroscopic data and comparison with literature. All the compounds were isolated from this species for the first time. The chemotaxonomic significance of the absence of sesquiterpene lactones in G. multifida has also been summarized.     

Two new carene-type monoterpenes from aerial parts of Ageratina adenophora

Two new carene-type monoterpenes, (1α,6α,7α)-8-hydroxy-2-carene-10-oic acid (1) and (1α,6α)-10-hydroxy-3-carene-2-one (2), were isolated from the aerial parts of Ageratina adenophora, together with a known monoterpene, (−)-isochaminic acid (3). The new structures were elucidated on the basis of extensive spectroscopic analysis, including MS, 1D and 2D NMR techniques. Compound 3 was isolated from A. adenophora for the first time. Compounds 2 and 3 were found to show anti-fungal activity against spore germination of Magnaporthe grisea with IC₅₀ values 0.623 and 0.503 mM, respectively.     

Two tirucallane derivatives from Paramignya scandens and their cytotoxic activity

Various chromatographic separations of the methanolic extract of Paramignya scandens stem and leaves resulted in the isolation of two new tirucallane derivatives, paramignyols A and B (1 and 2). Their structures were established by HR-ESI-MS, 1D and 2D NMR experiments, as well as, comparison with literature data. Compounds 1 and 2 showed significant cytotoxic activity (IC₅₀s ∼ 3.55–10.50 μM) on four tested human cancer cell lines: KB (epidermoid carcinoma), SK-Mel-2 (melanoma), LU-1 (lung adenocarcinoma), and MCF7 (breast cancer). This is the first report on chemical constituents and biological activities of P. scandens.